<p>Sputum IL-26 Is Overexpressed in Severe Asthma and Induces Proinflammatory Cytokine Production and Th17 Cell Generation: A Case–Control Study of Women</p>

Abstract

Objective: Asthma inflammation is a complex pathway involving numerous mediators. Interleukin-26 (IL-26), a member of the IL-10 cytokine family, is abundant in human airways and induces the production of proinflammatory cytokines. Our aim was to investigate the possible role of IL-26 in severe asthma. We analysed the expression of IL-26 in severe asthma both in peripheral blood and induced sputum. Patients and Methods: A total of 50 adult women with severe asthma were recruited and compared to 30 healthy controls (HC). Serum and sputum fluid (SF) levels of IL-26 and IL-17 were defined by ELISA. IL-26 mRNA expression and IL-26 protein were analysed using RT-PCR and Western blot. In vitro, we studied the effect of recombinant IL-26 (rIL-26) and SF-IL-26 on cultured CD4 + T cells and monocytes, comparing patients and controls. Results: Concentrations of IL-26 are higher in serum and induced sputum of asthmatic patients than in HC. Moreover, IL-26 protein and mRNA expression were significantly elevated in asthma sputum cells compared to PBMCs. We observed a positive correlation between body mass index (BMI) and sputum fluid IL-26, while the correlation between IL-26 and lung function tests (FEV1% and FEV1/FVC ratio) was negative. IL-17A was highly expressed in SF and correlated positively with IL-26. In patients' sputum IL-26 and IL-17A were significantly associated with neutrophils. Stimulation of cultured CD4 + T cells with monocytes by recombinant IL-26 promoted the generation of RORγt + Th17 + cells inducing the production of IL-17A, IL-1β, IL-6 and TNF-α cytokines. IL-26 expressed in SF was biologically active and induced IL-17 secretion in the presence of IL-1β and IL-6 cytokines. Conclusion: These findings show that IL-26 is highly produced in asthmatic sputum, induces pro-inflammatory cytokine secretion by monocytes/macrophages, and favours Th17 cell generation. IL-26 thereby appears as a novel pro-inflammatory cytokine, produced locally in the airways that may constitute a promising target to treat asthma inflammatory process.

Interleukin-26 Expression in Inflammatory Bowel Disease and Its Immunoregulatory Effects on Macrophages

“…IL-26 enhances the production and expression of pro-inflammatory cytokines and chemokines in human monocytes, epidermal keratinocytes, intestinal epithelial cells and colonic subepithelial myofibroblasts (SEMFs) ( 5 , 6 , 8 , 11 ). In particular, IL-26 promotes Th17 cell production ( 6 , 9 ), and these cells in turn produce IL-26, leading to a detrimental amplification loop that contributes to Th17-associated inflammation. Importantly, compared with control mice, transgenic mice expressing human IL-26 exhibit exacerbated skin inflammation as well as increased vascularization and infiltration by neutrophils and CD4 + T cells, and these effects are attenuated by anti-IL-26 monoclonal antibody administration ( 14 , 15 ).…”

The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene Modules

“…In “Neutrophils-Type” and “Interferon-Th1” (non-Th2) phenotype, interleukin-26 (IL26)-related function was upregulated and related to the severity of asthma. IL-26 is a member of IL-10 cytokine family, is abundant in human airways, and induces the production of pro-inflammatory cytokines ( Louhaichi et al, 2020 ). Stimulation of cultured CD4 + T cells with monocyte by recombining IL-26 promoted the generation of RORγ Th17 + cells, inducing the production of IL-17A, IL-1β, IL-6, and TNF-α ( Louhaichi et al, 2020 ).…”

“…IL-26 is a member of IL-10 cytokine family, is abundant in human airways, and induces the production of pro-inflammatory cytokines ( Louhaichi et al, 2020 ). Stimulation of cultured CD4 + T cells with monocyte by recombining IL-26 promoted the generation of RORγ Th17 + cells, inducing the production of IL-17A, IL-1β, IL-6, and TNF-α ( Louhaichi et al, 2020 ). Therefore, IL-26 could appear as a novel pro-inflammatory cytokine, produced in airways, and may be a promising target to treat inflammatory asthma.…”

A comprehensive review of IL‐26 to pave a new way for a profound understanding of the pathobiology of cancer, inflammatory diseases and infections

“…The elevated level of IL-26 in asthmatic patients was negatively correlated with lung function parameters, that is FEV1% and FEV1/FVC ratio, and conversely, its level was linked to neutrophil accumulation in the lung. Stimulation of cultured CD4 + T cells with IL-26 has led to the generation of IL-1β, IL-6, IL-17A and TNF-αproducing RoRγt + IL-17 + T cells, which promoted the development of severe asthma [36].…”